Fatty acid synthase (FAS) is a multifunctional enzyme that catalyzes the synthesis of long-chain fatty acids from small carbon substrates. The enzyme contains six separate enzymatic pockets along with an acyl carrier protein, which act sequentially to perform repeated condensations of acetyl CoA and malonyl CoA, yielding predominantly palmitate, a sixteen-carbon polyunsaturated fatty acid. Following seven such condensation cycles, palmitate remains covalently attached to the acyl carrier protein of the enzyme until it is liberated by the final enzymatic pocket on the enzyme, the intrinsic thioesterase.
Fatty acid synthesis has long been thought unimportant in most normal tissues, and the enzyme is down-regulated by dietary lipid. However, increased FAS expression and activity in tumors is well documented. Tumor cell dependence on de novo fatty acid synthesis is viewed as a metabolic anomaly, with the endogenously-synthesized fatty acids apparently incorporated into membrane phospholipids in preparation for cell division.
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